E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hemophilia A or Hemophilia B |
Emofilia A o Emofilia B |
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E.1.1.1 | Medical condition in easily understood language |
Hemophilia is an inherited bleeding disorder in which the blood does not clot normally and can result in internal bleeding into the muscles and joints. |
L'emofilia è un disordine emorragico ereditato in cui il sangue non coaugula normalmente e può provocare sanguinamenti interni nei muscoli e nelle articolazioni. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060614 |
E.1.2 | Term | Hemophilia B (Factor IX) |
E.1.2 | System Organ Class | 100000004850 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060613 |
E.1.2 | Term | Hemophilia A (Factor VIII) |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of fitusiran compared to on demand treatment with factor concentrates, as determined by the frequency of bleeding episodes. |
Valutare l'efficacia di fitusiran rispetto a un trattamento al bisogno con concentrati di fattore, determinata dalla frequenza di episodi emorragici. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of fitusiran compared to on demand treatment with factor concentrates, as determined by the frequency of spontaneous bleeding episodes, the frequency of joint bleeding episodes in patients, and health related quality of life (HRQOL) in patients receiving fitusiran. |
Valutare l'efficacia di fitusiran rispetto a un trattamento al bisogno con concentrati di fattore, determinata dalla frequenza di episodi di emorragia spontanea, frequenza di episodi di emorragia articolare, qualità di vita correlata allo stato di salute (HRQOL) nei pazienti che ricevono fitusiran. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Males ≥12 years of age; - Severe hemophilia A or B (evidenced by a central laboratory FVIII <1% or FIX level ≤2% at Screening) without inhibitors (evidenced by inhibitor titer of <0.6 BU/mL and supported by medical records); - AT activity ≥60% at Screening - A minimum of 6 bleeding episodes requiring factor concentrate treatment within the last 6 months - Willing and able to comply with the study requirements and to provide written informed consent and assent in the case of patients under the age of legal consent |
- Soggetti di sesso maschile di ≥12 anni di età - Emofilia A o B grave (FVIII <1% o livello FIX ≤2% allo Screening dimostrato da un laboratorio centrale) senza inibitori (con titolo degli inibitori < 0.6 BU/mL o come dimostrato dalle cartelle cliniche); - Attività AT ≥60% allo screening - Almeno 6 episodi di sanguinamento che hanno richiesto trattamento con concentrati di fattore negli ultimi 6 mesi - Volontà e capacità di aderire ai requisiti dello studio e di fornire il consenso informato scritto e l'assenso nel caso di pazienti al di sotto dell'età per fornire il consenso legale
|
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E.4 | Principal exclusion criteria |
- Patients with known co-existing bleeding disorders other than hemophilia A or B; - Patients with clinically significant liver disease; - Patients known to be HIV positive and have a CD4 count <200 cells/μL; - Patients with a history of arterial or venous thromboembolism - Estimated glomerular filtration rate ≤45 mL/mi /1.73m2 (using the Modification of Diet in Renal Disease [MDRD] formula) - Patients with a co-existing thrombophilic disorder - Patients with a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc - Patients with a history of intolerance to SC injection(s) - Patients with an anticipated or planned need for surgery during the study - Any other conditions or comorbidities that would make the patient unsuitable for enrollment or could interfere with participation in or completion of the study, per Investigator judgment |
- Pazienti con problemi di sanguinamento noti concomitanti diversi dall'emofilia A o B; - Pazienti con malattia epatica clinicamente significativa; - Pazienti con positività nota all'HIV e una conta CD4 <200 cellule/μL; - Pazienti con anamnesi di tromboembolia arteriosa o venosa; - Velocità di filtrazione glomerulare stimata ≤45 mL/minuto /1.73m2 (utilizzando la formula di modifica della dieta nella malattia renale [Modification of Diet in Renal Disease [MDRD] formula] - Pazienti con disturbo trombofilico concomitante; - Pazienti con anamnesi di molteplici allergie a farmaci o anamnesi di reazione allergica a un oligonucleotide o GaINAc; - Pazienti con anamnesi di intolleranza alle iniezioni SC; - Pazienti con necessità prevista o pianificata di intervento chirurgico nel corso dello studio; - Qualsiasi altra condizione o cormobilità che renderebbe il paziente non idoneo all'arruolamento o potrebbe interferire con la partecipazione allo studio o con il completamento dello stesso, secondo il giudizio dello Sperimentatore. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Annualized bleeding rate (ABR) |
Tasso annuale di sanguinamento |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Annualized spontaneous bleeding rate Annualized joint bleeding rate Haem-A-QOL score |
Tasso annuale di sanguinamento spontaneo Tasso annuale di sanguinamento articolare Variazione del punteggio Haem-A-QOL |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Terapia standard |
Rescue SOC |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Bulgaria |
Canada |
China |
Denmark |
France |
Germany |
Hungary |
India |
Ireland |
Israel |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Netherlands |
Portugal |
Russian Federation |
South Africa |
Spain |
Taiwan |
Turkey |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |